Iron chelation is a medical process that removes excess iron from the body using specialized compounds called chelating agents. The human body tightly regulates iron absorption but lacks a programmed physiological mechanism for excreting large amounts of the mineral. When iron accumulates beyond the body’s storage capacity, it can become toxic, requiring external intervention to prevent organ damage. This procedure is generally reserved for individuals with severe iron overload.
Conditions Requiring Iron Chelation
Iron chelation therapy is primarily used to treat iron overload, also known as hemosiderosis, which results from two main causes. The most common cause is secondary iron overload, developing in patients who receive frequent blood transfusions. Since the body cannot excrete the significant iron contained in each unit of red blood cells, it accumulates in organs. Conditions like beta-thalassemia, sickle cell disease, and myelodysplastic syndromes (MDS) often require chronic transfusions, leading to iron buildup in the heart, liver, and endocrine glands.
Hereditary hemochromatosis, a genetic disorder, is the other major cause of iron overload. In this condition, the body absorbs an abnormally high amount of dietary iron, which then deposits in various tissues. Chelation is initiated when iron levels exceed safe limits, often indicated by serum ferritin levels above 1,000 ng/mL, to prevent organ failure and premature death.
The Chemical Process of Chelation
The term “chelation” is derived from the Greek word chele, meaning “claw,” describing the chemical action. A chelating agent is a molecule that wraps around a metal ion, such as trivalent ferric iron (\(\text{Fe}^{3+}\)), forming multiple chemical bonds to create a ring-like structure. This binding action traps the iron, rendering it chemically inert and non-toxic.
The resulting complex is water-soluble, which is crucial for detoxification, allowing the body to safely excrete the complex. Depending on the specific chelator, the iron-chelator complex is eliminated primarily through the kidneys via urine or the liver via bile and feces. This mechanism prevents free iron from participating in harmful chemical reactions that cause oxidative stress and tissue damage.
Medical Iron Chelation Therapy
Medical chelation is the most direct and effective method for removing excessive iron stores from the body using pharmaceutical agents. Three primary drugs are approved for this purpose, each with a different route of administration and profile. Deferoxamine (DFO) is the oldest agent and must be administered parenterally, typically through a slow subcutaneous or intravenous infusion using a portable pump over eight to twelve hours several times a week. While highly effective, the required infusion schedule can make adherence challenging for many patients.
Deferasirox (DFX) is an oral chelator that offers the convenience of once-daily dosing, significantly improving patient quality of life and compliance. It is available in a tablet form that is dissolved in water or juice and is generally used for chronic iron overload. The starting dose is usually around 20 mg per kilogram of body weight per day, which is then adjusted based on liver iron concentration (LIC) and serum ferritin levels.
Deferiprone (DFP) is another oral agent, often used in combination with Deferoxamine, particularly when there is evidence of iron accumulation in the heart. This drug works by chelating iron inside cells, but its use requires careful monitoring due to a potential side effect of agranulocytosis, which necessitates regular blood cell counts. Treatment with any of these agents requires ongoing monitoring of iron levels, often through blood tests for serum ferritin and MRI scans to measure iron concentration in the liver and heart.
Dietary Strategies to Influence Iron Levels
While dietary adjustments cannot replace medical chelation for severe overload, they can play a supportive role in managing iron intake and absorption. Certain compounds naturally found in foods act as inhibitors, reducing the amount of iron the digestive system absorbs from a meal. Phytic acid, or phytate, is one such inhibitor found in whole grains, legumes, nuts, and seeds, which binds to iron in the gut.
Polyphenols and tannins, abundant in black tea, coffee, and cocoa, also significantly impair iron absorption by forming insoluble complexes with the mineral. Consuming these beverages with iron-containing meals can reduce non-heme iron uptake by as much as 60%. Calcium, found in dairy products and supplements, is another substance that can inhibit the absorption of both heme and non-heme iron when consumed in amounts between 300 to 600 milligrams.
Patients are often advised to limit high-iron foods, such as red meat and iron-fortified cereals, and to avoid cooking in cast-iron pans. Some natural compounds, including curcumin (from turmeric) and green tea extract (EGCG), demonstrate mild iron-chelating and antioxidant properties in laboratory settings. These supplements are sometimes explored for their potential to reduce non-transferrin bound iron (NTBI), but they must be used only as an adjunct to prescribed medical chelation therapy under strict medical guidance.